Abstract
Peroxiredoxin1 (Prdx1) is an antioxidant enzyme belonging to the peroxiredoxin family of proteins. Prdx1 catalyzes the reduction of H2O2 and alkyl hydroperoxide and plays an important role in different biological processes. Prdx1 also participates in various age-related diseases and cancers. In this study, we investigated the role of Prdx1 in pronephros development during embryogenesis. Prdx1 knockdown markedly inhibited proximal tubule formation in the pronephros and significantly increased the cellular levels of reactive oxygen species (ROS), which impaired primary cilia formation. Additionally, treatment with ROS (H2O2) severely disrupted proximal tubule formation, whereas Prdx1 overexpression reversed the ROS-mediated inhibition in proximal tubule formation. Epistatic analysis revealed that Prdx1 has a crucial role in retinoic acid and Wnt signaling pathways during pronephrogenesis. In conclusion, Prdx1 facilitates proximal tubule formation during pronephrogenesis by regulating ROS levels.
Highlights
Peroxiredoxin[1] (Prdx1) is an antioxidant enzyme belonging to the peroxiredoxin family of proteins
Whole-mount in situ hybridization analysis at different developmental stages (NF stage 8, 14, 16, 22 and 33) showed that prdx[1] was highly and predominantly expressed in the forebrain, eye, multiciliated cells, and pronephros of developing embryos (Fig. S1B). prdx[1] was expressed in the intermediate mesoderm, which comprises the proximal compartments that develop into the proximal tubules (Fig. S1B)
The decreased expression of lim[1], pax2,smp[30] and pax[8] was rescued by co-injection with prdx1* RNA (Fig. 3A,B). These results indicate that Prdx[1] functions as a one of significant modulator of retinoic acid (RA) signaling for pronephrogenesis
Summary
Peroxiredoxin[1] (Prdx1) is an antioxidant enzyme belonging to the peroxiredoxin family of proteins. Three main structures are formed during kidney development, namely, the pronephros, mesonephros, and metanephros[3], all of which originate from the intermediate mesoderm during embryogenesis[4]. Several signaling cascades, including bone morphogenetic protein, fibroblast growth factor, notch, Wnt, and retinoic acid (RA) pathways[4], are involved in pronephros development. Evidence indicates that canonical Wnt signaling plays an important role in kidney development, and inhibition of Wnt signaling impedes pronephros development in amphibians[8]. Prdx proteins catalyze the reduction of different peroxide substrates, and are crucial for H2O2-mediated cell signaling[17]. Prdx[1] through 6 possess conserved cysteine residues and undergo oxidation–reduction cycles[18] In addition to their functions as antioxidants, Prdx proteins are involved in various physiological processes[19, 20]
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